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  • 1.
    Baghdassarian, Eva Juselius
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Nilsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Brainstem Audiometry Evoked Response (BAER) Profiling. New Potential Biomarkers in Schizoaffective Disorder and Early Psychosis2016In: Early Intervention in Psychiatry, ISSN 1751-7885, E-ISSN 1751-7893, Vol. 10, p. 160-160Article in journal (Other academic)
  • 2.
    Baghdassarian, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Nilsson, Maria Markhed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Nilsson, Björn M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Auditory brainstem response (ABR) profiling tests as diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD)2018In: Acta Neuropsychiatrica, ISSN 0924-2708, E-ISSN 1601-5215, Vol. 30, no 3, p. 137-147Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the performances of two auditory brainstem response (ABR) profiling tests as potential biomarkers and diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD), respectively, in an investigator-initiated blinded study design.

    Method: Male and female patients with schizophrenia (n=26) and adult ADHD (n=24) meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) diagnostic criteria and healthy controls (n=58) comprised the analysis set (n=108) of the total number of study participants (n=119). Coded sets of randomized ABR recordings were analysed by an independent party blinded to clinical diagnoses before a joint code-breaking session.

    Results: The ABR profiling test for schizophrenia identified schizophrenia patients versus controls with a sensitivity of 84.6% and a specificity of 93.1%. The ADHD test identified patients with adult ADHD versus controls with a sensitivity of 87.5% and a specificity of 91.4%.

    Conclusion: The ABR profiling tests discriminated schizophrenia and ADHD versus healthy controls with high sensitivity and specificity. The methods deserve to be further explored in larger clinical studies including a broad range of psychiatric disorders to determine their utility as potential diagnostic biomarkers.

  • 3.
    Edvinsson, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bingefors, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gender differences of axis I and II comorbidity in subjects diagnosed with attention-deficit hyperactivity disorder as adults2013In: Acta Neuropsychiatrica, ISSN 0924-2708, E-ISSN 1601-5215, Vol. 25, no 3, p. 165-174Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate gender differences in psychiatric comorbidity patients diagnosed with attention-deficit hyperactivity disorder (ADHD) as adults. Methods: Interviews about current ADHD symptoms and psychiatric comorbidity on axis I and II (Structured Clinical Interview for DSM-IV axis I and axis II) were conducted in a clinical cohort of 168 patients (78 women, 90 men). Independent information on childhood and current symptoms was collected from parents, partners and patient files. Results: The lifetime prevalence of psychiatric comorbidity on axis I reached 92%, and current comorbidity, including autism spectrum disorders and Tourette's syndrome, was 47%. Women had a higher lifetime prevalence of mood and eating disorders compared with men, where substance-use disorders were more frequent. Ten per cent of patients fulfilled diagnostic criteria for a personality disorder. When excluding the general diagnostic criteria, 46% of the patients endorsed the specific criteria for at least one personality disorder. Gender differences were identified with predominance of histrionic personality traits in women and conduct disorder in men. Conclusion: Patients diagnosed with ADHD as adults display an extremely high lifetime axis I comorbidity with a gender-specific pattern similar to the general population. No gender differences were identified with regard to personality disorders; however, an increased prevalence of deviant personality traits was confirmed. This study stresses the importance of evaluating comorbidity among patients diagnosed with ADHD as adults to secure optimal treatment.

  • 4.
    Färdig, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Melin, Lennart
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Mueser, Kim
    Center for Psychiatric Rehabilitation, Boston University, MA, USA.
    Neurocognitive functioning and outcome of the Illness Management and Recovery Program for clients with schizophrenia and schizoaffective disorder2016In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 6, p. 430-435Article in journal (Refereed)
    Abstract [en]

    The relationship between psychosocial programming and neurocognition has been established in previous research, but has not been explored in the context of the Illness Management and Recovery Program (IMR). This study examined associations between neurocognition and illness self-management skills acquisition, based on two previous trials of IMR. Neurocognitive functioning was assessed at baseline and post-treatment in 53 participants with schizophrenia or schizoaffective disorder who completed the IMR. Illness self-management was measured by the client and clinician versions of the Illness Management and Recovery Scale. Statistical analyses investigated improvements in neurocognitive functioning and possible association between illness self-management skills acquisition and neurocognitive functioning. Speed of processing as measured by the Trail Making Test A, was related to client-reported acquisition of illness self-management skills, before and after controlling for psychiatric symptoms and medication, but did not predict improvement in clinician ratings of client illness self-management skills. However, when controlling for client session attendance rates, the association between speed of processing and client-reported illness self-management skills acquisition ceased to be statistically significant, which suggests that compromised neurocognitive functioning does not reduce response to training in illness self-management in itself. The association between the frequency of attended IMR sessions and outcome of the IMR seems to decrease the negative impact of compromised neurocognition on illness self-management skills acquisition. Also, clients with slower speed of processing may experience less benefit from the IMR and may attend fewer sessions.

  • 5.
    Färdig, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Melin, Lennart
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Tommy, Lewander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Symptom severity and outcome of the Illness Management and Recovery (IMR) program for schizophrenia and schizoaffective disorderManuscript (preprint) (Other academic)
    Abstract [en]

    The present study explored the effects of the Illness Management and Recovery program on the severity criterion of symptomatic remission in schizophrenia and schizoaffective disorder, and whether participants meeting the severity criterion experienced greater improvement in the outcomes of the IMR program. The results suggest that significantly more participants met the severity criterion at post-treatment. Improvements in general psychopathology, self-rated and clinician rated illness self-management, and subjective satisfaction with life, were found for the total sample. Although demonstrating significantly higher levels of general psychopathology, compared to participants meeting the severity criterion, it appears that participants not meeting the severity criterion also benefited from the IMR program, as indicated by the similar effect sizes of the two subgroups (meeting versus not meeting the severity criterion at post-treatment).

  • 6.
    Färdig, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Melin, Lennart
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Evaluation of the Illness Management and Recovery Scale in schizophrenia and schizoaffective disorder2011In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 132, no 2-3, p. 157-164Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the psychometric properties of the parallel client and clinician versions of the Illness Management and Recovery Scale (IMRS) developed to monitor the clients' progress in the Illness Management and Recovery (IMR) program in schizophrenia. A total of 107 study participants completed assessments of the IMRS, interview-based ratings of psychiatric symptoms, self-ratings of psychiatric symptoms, perception of recovery, and quality of life. Case managers completed the clinician version of the IMRS. Both versions of the scale demonstrated satisfactory internal reliability and strong test-retest reliability. The results also indicated convergent validity with interview-based ratings of psychiatric symptoms, self-rated symptoms, perception of recovery, and quality of life for both versions of the IMRS. These findings support the utility of the IMRS as a measure of illness self-management and recovery in clients with schizophrenia.

  • 7.
    Färdig, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Melin, Lennart
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Folke, Fredrik
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    A Randomized Controlled Trial of the Illness Management and Recovery Program for Persons With Schizophrenia2011In: Psychiatric Services, ISSN 1075-2730, E-ISSN 1557-9700, Vol. 62, no 6, p. 606-612Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the study was to evaluate the effects of the illness management and recovery (IMR) program on symptoms and psychosocial functioning of individuals with schizophrenia or schizoaffective disorder in an outpatient setting in Sweden. Methods: A total of 41 persons with schizophrenia or schizoaffective disorder who were receiving treatment at six psychiatric outpatient rehabilitation centers were randomly assigned to either an IMR group for nine months or to treatment as usual (control condition). Assessments were conducted at baseline, posttreatment (nine months), and follow-up (21 months) and included self-reports and ratings by clinicians (both blind and nonblind to treatment assignment) of illness management, psychiatric symptoms, recovery, coping, quality of life, hospitalization, insight, and suicidal ideation. Results: As measured by self-report and ratings of nonblinded clinicians, IMR program participants demonstrated significantly greater improvement in illness management than participants in the control condition. Ratings of psychiatric symptoms by blinded clinicians using the Psychosis Evaluation Tool for Common Use by Caregivers and self-reported ratings of psychosocial functioning on the Ways of Coping Questionnaire also showed better outcomes than for participants in treatment as usual. A statistically significant decrease in suicidal ideation between baseline and follow-up was found for IMR program participants. Conclusions: The study supports previous findings and suggests that the IMR program is effective in improving the ability of individuals with schizophrenia to better manage their illness.

  • 8. Kallstrand, Johan
    et al.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Baghdassarian, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Nielzen, Soren
    A new method for analyzing auditory brain-stem response waveforms using a moving-minimum subtraction procedure of digitized analog recordings2014In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 10, p. 1011-1016Article in journal (Refereed)
    Abstract [en]

    The auditory brain-stem response (ABR) waveform comprises a set of waves (labeled I-VII) recorded with scalp electrodes over 10 ms after an auditory stimulation with a brief click sound. Quite often, the waves are fused (confluent) and baseline-irregular and sloped, making wave latencies and wave amplitudes difficult to establish. In the present paper, we describe a method, labeled moving-minimum subtraction, based on digitization of the analog ABR waveform (154 data points/ms) in order to achieve alignment of the ABR response to a straight baseline, often with clear baseline separation of waves and resolution of fused waves. Application of the new method to groups of patients showed marked differences in ABR waveforms between patients with schizophrenia versus patients with adult attention deficit/hyperactivity disorder versus healthy controls. The findings show promise regarding the possibility to identify ABR markers to be used as biomarkers as support for clinical diagnoses of these and other neuropsychiatric disorders.

  • 9.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ehrnebo, M
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Trolin, C G
    Bäckström, T
    Panagiotidis, G
    Spira, J
    Nyström, C
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 124-132Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).

    MATERIALS AND METHODS:

    A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.

    RESULTS:

    Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.

    CONCLUSIONS:

    Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.

  • 10.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gomes-Trolin, Cecilia
    Bäckström, Tobias
    Panagiotidis, Georgios
    Ehrnebo, Mats
    Nyström, Christer
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers2012In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 35, no 3, p. 111-117Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration.

    METHODS: A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.

    RESULTS: The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence.

    CONCLUSIONS: The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.

  • 11.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lewander, Tommy
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    LeWitt, Peter A.
    Lundqvist, Christofer
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Enteral Levodopa/Carbidopa infusion in advanced Parkinson disease: Long-term exposure2008In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 31, no 2, p. 63-73Article in journal (Refereed)
    Abstract [en]

    Objectives: In patients with advanced Parkinson disease, levodopa/carbidopa formulated as a gel suspension (Duodopa) permits continuous delivery into the small intestine using a portable pump, resulting in less variability in levodopa concentrations and fewer motor fluctuations and dyskinesias than with oral levodopa administration. This is a retrospective analysis of the long-term clinical experience with this agent. Methods: All but 1 of the patients who had received enteral levodopa infusion treatment between January 1, 1991, and June 30, 2002, consented to a review of their hospital charts. Results: Of the 65 patients with initial testing of the treatment, 86% opted for continued treatment via percutaneous endoscopic gastrostomy or gastrojejunostomy. Total exposure to levodopa infusion was 216 patient-years (mean, 3.7 years). Maximum treatment duration was 10.7 years. Fifty-two patients were treated for 1 year or longer. The adverse effect profile of levodopa/carbidopa infusion was similar to that observed with oral administration of levodopa. Seven deaths occurred, all considered unrelated to the treatment. Intestinal tube problems, including dislocation of the intestinal tube to the stomach, were the most common technical problem, occurring in 69% of the patients during the first year. The optimal daily dose of levodopa decreased by an average of 5% during follow-up. Conclusions: The safety of enteral infusion of levodopa/ carbidopa formulated as a gel suspension was found acceptable. For most patients, the technical challenges posed by the enteral infusion system were offset by the improvement in motor fluctuations and dyskinesias offered by this technique.

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